Abstract
The ATP binding cassette (ABC) E1 (ABCE1), a member of the ABC family, was originally described as the RNase L inhibitor. Through forming a heterodimer with RNase L, ABCE1 participates in the negative regulation of the 2-5A/RNase L system and thus mediates a wide range of biological functions. Recent evidence has shown the new roles of ABCE1 in tumorigenesis. However, there have been no investigations on the specific effect of ABCE1 on glioma. In the present study, we examined the expression pattern and possible role of ABCE1 in glioma. Our study demonstrated that ABCE1 was up-regulated in glioma tissues and cell lines. Down-regulation of ABCE1 inhibited temozolomide (TMZ) resistance of glioma cells in vitro and in vivo. In addition, we found that the PI3K/Akt/NF-κB pathway was involved in ABCE1-mediated chemoresistance of glioma cells. Taken together, our study suggested ABCE1 as a promising target for glioma chemotherapy.
Highlights
Glioma, a common type of brain tumor, accounts for ∼30% of cancers in the central nervous system [1,2]
The results revealed that the mRNA and protein expression of ABC E1 (ABCE1) were markedly up-regulated in U87 and A172 cells in comparison with the normal human astrocyte (NHA) (Figure 1C,D)
The results showed that the IC50 value of TMZ was remarkably reduced in ABCE1-knockdown U87 and A172 cells in comparison with the control cells (Figure 2C,D)
Summary
A common type of brain tumor, accounts for ∼30% of cancers in the central nervous system [1,2]. Many therapeutic approaches for glioma have been improved, the treatment effect is unsatisfactory and the median survival time of glioma patients is still less than 12 months [3,4]. This dismal situation desperately demands a variety of novel therapies. Recent studies showed that the therapeutic efficiency of TMZ is limited due to chemoresistance in tumors, which has become a serious impediment in glioma treatment [8,9,10,11,12]. It is urgently needed to better understand the mechanisms underlying TMZ resistance in order to improve the poor outcome of glioma patients
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